A polymorphism in CNR1 (rs2180619, A>G) seems to influence affective working memory. People with the most prevalent A allele are biased towards remembering positive words rather than negative words. People with the G allele on the other hand have a better affective working memory in general (Fairfield et al., 2017).

ATP-binding cassette /ABC transporters are involved in shuttling many substances across the plasma membrane, including cannabinoids like THC. In ABCB1, the C3435T (rs1045642) was found to modulate serum THC levels in the sense that heavy cannabis users carrying the T allele had significantly lower THC levels (8 ng/ml) than CC homozygotes (15.7 ng/ml) (Kebir et al., 2017).

Variations the Cyp2C9 gene are associated with different THC metabolism. The Cyp2C9*2 was neutral to THC degradation but Cyp2C9*3 slowed THC degradation down threefold and decreased THC metabolite 11-COOH-THC levels by 70% compared to Cyp2C9*1 (Sachse-Seeboth et al., 2009).

Cannabis dependence

Two polymorphisms for FAAH, rs324420 and rs4141964, were associated with an increased risk of developing cannabis dependence. For other ECS genes such as CNR1, MAGL and DAGL no such association was found (Melroy-Greif et al., 2016).

Carriers of the C allele for the CNR1 rs806374 polymorphism have an increased risk of developing cannabis dependence (Ashenhurst et al., 2017).

There is an increased risk of developing cyclic vomiting syndrome for people carrying the G allele of the CNR1 rs806380 polymorphism and a reduced risk for people with the CC phenotype for CNR1 rs806368 or those carrying the G allele of the rs1799971 polymorphism of the Mu-opioid receptor (Wasilewski et al., 2017). In addition, the Mu-opioid receptor rs1799971 G allele and the CNR1 rs806368 C allele were associated with migraine. The C allele of CNR1 rs2023239 was associated with positive outcome of treatment (Wasilewski et al., 2017).

A CNR1 mutation, G1359A is associated with esophageal cancer, with the A allele being more prevalent in tissue samples from cancer patients and the A allele being negatively correlated with survival time (Bedoya et al., 2009).

Glioma

The G allele of CNR1 G1359A is associated with a lower susceptibility to glioma (Núñez et al., 2010). Interestingly, this mutation is also associated with reduced cardiovascular risk (de Luis et al., 2016).

Happiness

One polymorphism in CNR1, rs806377, is associated with subjective happiness with carriers of the C allele responding stronger to positive stimuli and experiencing a higher subjective happiness level than homozygous carriers of the T allele (Matsunaga et al., 2014).

HIV/Hepatitis C co-infection

The CNR2 polymorphism rs35761398 was investigated in patients with HIV/Hepatitis C co-infection. Patients with the R allele being significantly more associated with inflammatory liver damage than the Q allele (Sagnelli et al., 2017).

Irritable bowel syndrome/IBS

The CNR1 gene encoding CB1 varies in the amount of AAT triplet repeats. People with more than 10 AAT repeats had a significantly higher risk of developing IBS than people with fewer AAT repeats (Jiang et al., 2014).

However, no correlation was found between the number of AAT triplets and the disease phenotype: constipation, diarrhea or mixed (Camilleri et al., 2013).

Variation in FAAH (rs324420, C385A), was found to be associated with irritable bowel syndrome and IBS-diarrhea and IBS-alternating in particular (Camilleri et al., 2008), although this is disputed (Jiang et al., 2014).

multiple sclerosis treatment with interferon-beta is often discontinued when patients develop the ‘flu-like syndrome’. Patients with the GG genotype of the TRPV1 rs222747 polymorphism report greater pain and weakness during flu-like syndrome and are thus more likely to discontinue interferon-beta treatment (Buttari et al., 2017).

Non-alcoholic Fatty Liver Disease/NAFLD

NAFLD is often associated with Polycystic Ovary Syndrome/PCOS. The G allele of CNR1 rs806381 and the GG phenotype of rs10485170 were significantly higher in women with PCOS and NAFLD than in PCOS women without NAFLD (Kuliczkowska Plaksej et al., 2014).

N-Acylethanolamine acid amidase (NAAA) is a lysosomal enzyme, hydrolyzing various bioactive N-acylethanolamines with a preference for palmitoylethanolamide. In the human Prostate cancer cell line LNCaP, four splice variants were found. Two of these splice variants, b2 and c2, form catalytically inactive, truncated proteins which may be associated with the risk of developing Prostate cancer (Sakura et al., 2016).

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